Confounding by indication: The case of calcium channel blockers

Purpose - To review conceptual issues regarding confounding by indication i n the context of studies of calcium channel blockers (CCBs). Methods - Review of literature, with special attention to two articles in t he current issue. Results - Conflicting arguments about the presence of uncontrollable confou nding by indication in studies of CCBs are reviewed and criticized. Studies with potential confounding by indication can benefit from appropriate anal ytic methods, including separating the effects of a drug taken at different times, sensitivity analysis for unmeasured confounders, and instrumental v ariables and G-estimation. Conclusions - Whether confounding by indication accounts for observed assoc iations is often difficult to determine; this is the case in studies of CCB s. When confounding by indication is suspected, a variety of methods to dea l with it may be useful. Copyright (C) 2000 John Wiley & Sons, Ltd.